LET'S TALK ABOUT SEMEN

Slightly unsavory (and certainly salacious), the subject of semen is seldom suitable for social settings. But why are we so shy about semen? Scientifically speaking—it’s a pretty spectacular substance.Besides containing sperm, semen is also comprised of various goodies secreted from the seminal vesicle glands, including proteins, mucus, and even the fructose that supplies energy to the sperm! One especially important component is Semenogelin I (SEMG1), the predominant protein found in semen.1

Each ejaculation releases >100 million sperm cells, but only one sperm succeeds in fertilizing the egg.[2] SEMG1 helps it get there.

Immediately following ejaculation, SEMG1 aggregates with epididymal protease inhibitor (EPPIN) and fibronectin, causing semen to become temporarily gelatinous.3 This physically immobilizes the sperm, and SEMG1 and EPPIN further inhibit sperm motility by affecting the intracellular calcium and pH levels in sperm.4

Why does semen coagulate? Maybe to prevent sperm “backflow”. Or, species with more promiscuous females (like chimpanzees) tend to have thicker coagulum; so if another male mates with the female, his sperm might be blocked by the first male’s coagulum.[5] Image source: lkiwaner.

However, within 20 minutes, SEMG1 is enzymatically degraded into smaller protein fragments, causing the thick semen coagulum to liquefy… thereby freeing the sperm to swim onward towards the egg.3

That’s not the end of SEMG1’s role though; even as it gets broken down, its smaller fragments continue to be active in a variety of processes. For example, some SEMG1 fragments actually have anti-microbial properties, which protect the sperm as they travel through the relatively hostile female reproductive tract.3 Not all SEMG1 fragments are beneficial though; other fragments aggregate into amyloid fibrils that enhance HIV infections.6 In both cases though, the anti-microbial and HIV-enhancing properties are only temporary, since eventually, SEMG1 will be degraded into tinier, non-functional pieces, finally ending its stint as a protein “jack-of-all-trades”.

But Wait, There's More!

Increasing our understanding of reproductive processes is fascinating and instructive in itself, but studying SEMG1 could also lead to impactful applications—most excitingly, male birth control! Indeed, reversible sterility was successfully induced in macaque monkeys by manipulating EPPIN function!7 Because EPPIN and SEMG1 interactions inhibit sperm motility, EPPIN-SEMG1 binding sites are considered attractive targets for pharmacological intervention.8 Research, of course, is ongoing.

Another promising application is cancer diagnostics. SEMG1 may be most infamous for it’s role in semen, but it’s actually found all over the body. In the kidneys, SEMG1 expression is being pursued as a possible biomarker for renal cell carcinoma.9 Preliminary data demonstrates that even in the same patient, cells from malignant tumors have lower SEMG1 levels than in normal tissue; similarly, patients with SEMG1-negative tumors have a higher risk of cancer recurrence.9 In this case, SEMG1 could be used to predict cancer progression and severity. Confusingly though, SEMG1 might promote prostate cancer and has been detected in other malignancies like lung carcinoma, melanoma, and leukemias.10 SEMG1 might be expressed in many tissues, but it clearly doesn’t have the same function in each.

Far from mundane, SEMG1 is mysterious and fascinating, with diverse functions beyond its role in semen. And yet, despite having been discovered nearly 30 years ago,11 SEMG1 still has only 150 publications to its name. But really, how surprising is that? After all, how many grad students would feel comfortable telling their parents that they’re devoting the next 5+ years of their life to studying semen? Perhaps it’s time to end the stigma, and stop the shame. Share the love about SEMG1, and spread the word: science is pretty awesome… and so is semen.